View source for 1nki


==CRYSTAL STRUCTURE OF THE FOSFOMYCIN RESISTANCE PROTEIN A (FOSA) CONTAINING BOUND PHOSPHONOFORMATE==
<StructureSection load='1nki' size='340' side='right'caption='[[1nki]], [[Resolution|resolution]] 0.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1nki]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NKI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NKI FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 0.95&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PPF:PHOSPHONOFORMIC+ACID'>PPF</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1nki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nki OCA], [https://pdbe.org/1nki PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nki RCSB], [https://www.ebi.ac.uk/pdbsum/1nki PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nki ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FOSA_PSEAE FOSA_PSEAE] Metalloglutathione transferase which confers resistance to fosfomycin by catalyzing the addition of glutathione to fosfomycin.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nk/1nki_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1nki ConSurf].
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== Publication Abstract from PubMed ==
Fosfomycin [(1R,2S)-epoxypropylphosphonic acid] is a simple phosphonate found to have antibacterial activity against both Gram-positive and Gram-negative microorganisms. Early resistance to the clinical use of the antibiotic was linked to a plasmid-encoded resistance protein, FosA, that catalyzes the addition of glutathione to the oxirane ring, rendering the antibiotic inactive. Subsequent studies led to the discovery of a genomically encoded homologue in the pathogen Pseudomonas aeruginosa. The proteins are Mn(II)-dependent enzymes where the metal is proposed to act as a Lewis acid stabilizing the negative charge that develops on the oxirane oxygen in the transition state. Several simple phosphonates, including the antiviral compound phosphonoformate (K(i) = 0.4 +/- 0.1 microM, K(d) approximately 0.2 microM), are shown to be inhibitors of FosA. The crystal structure of FosA from P. aeruginosa with phosphonoformate bound in the active site has been determined at 0.95 A resolution and reveals that the inhibitor forms a five-coordinate complex with the Mn(II) center with a geometry similar to that proposed for the transition state of the reaction. Binding studies show that phosphonoformate has a near-diffusion-controlled on rate (k(on) approximately 10(7)-10(8) M(-1) s(-1)) and an off rate (k(off) = 5 s(-1)) that is slower than that for fosfomycin (k(off) = 30 s(-1)). Taken together, these data suggest that the FosA-catalyzed reaction has a very early transition state and phosphonoformate acts as a minimal transition state analogue inhibitor.

Phosphonoformate: a minimal transition state analogue inhibitor of the fosfomycin resistance protein, FosA.,Rigsby RE, Rife CL, Fillgrove KL, Newcomer ME, Armstrong RN Biochemistry. 2004 Nov 2;43(43):13666-73. PMID:15504029<ref>PMID:15504029</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1nki" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa PAO1]]
[[Category: Armstrong RN]]
[[Category: Newcomer ME]]
[[Category: Pharris RE]]
[[Category: Rife CL]]